This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.GENETIC ANALYSIS OF SUSCEPTIBILITY TO COPD EXACERBATIONS - PILOT STUDYI. BACKGROUND AND SIGNIFICANCEChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Cigarette smoking is the major known risk factor for the development of COPD; however, the development of airflow obstruction, the defining characteristic of COPD, is markedly variable among smokers (1). COPD exacerbations are periods of worsening respiratory symptoms that occur frequently in some COPD subjects, but rarely in other COPD subjects. COPD exacerbations are a major contributor to COPD-related morbidity and mortality. However, some COPD subjects have frequent COPD exacerbations, while other COPD subjects never have exacerbations.II.
SPECIFIC AIMS A. We will enroll African-American COPD patients in metropolitan Atlanta, GA for investigation of the epidemiologic and genetic determinants of COPD and COPD-related phenotypes. B. We will test variants in innate immunity genes for association with susceptibility to develop exacerbations of COPD.As a pilot study for a larger project, genetic variants will be compared in 10 COPD subjects with frequent exacerbations (cases) and 10 COPD subjects with infrequent exacerbations (controls) will be enrolled. III. SUBJECT SELECTION Frequent and infrequent COPD exacerbators will be identified from the medical and pulmonary clinics of Grady Memorial Hospital, and the ER admission logs and pulmonary function laboratory logs. All eligible subjects will be adults with the expectation that they will likely be at least 40 years of age. COPD patients will have severe smoking-related chronic obstructive pulmonary disease, defined as FEV1 d 50% predicted with FEV1/FVC 0.7, with at least 10 pack-years of cigarette smoking. Frequent COPD exacerbators will be subjects with at least two COPD exacerbations per year for the past three years; infrequent COPD exacerbators will be COPD cases with no COPD exacerbations in the past three years. Any woman who may be pregnant is not eligible to participate because pregnancy could interfere with spirometric measurements and to avoid administration of albuterol to pregnant women.Study volunteers will be enrolled, interviewed, and undergo study procedures at the Morehouse School of Medicine Clinical Research Center.
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